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DEFINITION AND PATHOGENESIS
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Disease of unknown etiology in which tissues and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes. Genetic, environmental, and sex hormonal factors are likely of pathogenic importance. T- and B-cell hyperactivity, production of autoantibodies with specificity for nuclear antigenic determinants, and abnormalities of T-cell function occur.
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CLINICAL MANIFESTATIONS
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Approximately 90% of pts are women, usually of child-bearing age; highest prevalence is in African-American and Afro-Caribbean women. Course of disease is often characterized by periods of exacerbation and relative quiescence. May involve virtually any organ system and have a wide range of disease severity. Common features include:
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Constitutional: fatigue, fever, malaise, weight loss
Cutaneous: rashes (especially malar “butterfly” rash), photosensitivity, vasculitis, alopecia, oral ulcers
Arthritis: inflammatory, symmetric, nonerosive
Hematologic: anemia (may be hemolytic), neutropenia, thrombocytopenia, lymphadenopathy, splenomegaly, venous or arterial thrombosis
Cardiopulmonary: pleuritis, pericarditis, myocarditis, endocarditis. Pts are also at increased risk of myocardial infarction usually due to accelerated atherosclerosis.
Nephritis: classification is primarily histologic (Table 349-2, in HPIM-20).
GI: peritonitis, vasculitis
Neurologic: organic brain syndromes, seizures, psychosis, cerebritis
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A clinical and immunologic picture similar to spontaneous SLE may be induced by drugs; in particular: procainamide, hydralazine, isoniazid, chlorpromazine, methyldopa, minocycline, TNF inhibitors. Features are predominantly constitutional, joint, and pleuropericardial; CNS and renal disease are rare. All pts have ANAs; antihistone antibodies may be present, but antibodies to dsDNA and hypocomplementemia are uncommon. Most pts improve following withdrawal of offending drug.
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History and physical examination
ANA present in >98% of pts, but a (+) ANA is not specific for SLE. Laboratory assessment should include: CBC, ESR, ANA and ANA subtypes (antibodies to dsDNA, ssDNA, Sm, anti-Ro/SS-A, anti-La/SS-B, histone), complement levels (C3, C4, CH50), serum immunoglobulins, VDRL, PT, PTT, anticardiolipin antibody, lupus anticoagulant, urinalysis.
Appropriate radiographic studies
ECG
Consideration of renal biopsy if evidence of glomerulonephritis
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Classification criteria used to confirm SLE in studies can provide a basis in individual pts for estimating the probability that a disease is SLE. Four or more published criteria carry a 93% specificity and 92% sensitivity for SLE (Table 349-3, in HPIM-20).
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TREATMENT Systemic Lupus Erythematosus
Choice of therapy is based on type and severity of disease manifestations. Goals are to control acute, severe flares and to develop maintenance strategies, whereby symptoms are suppressed to an acceptable level. Treatment choices depend on (1) whether disease is life threatening or likely to cause organ damage; (2) whether manifestations are reversible; and (3) the best approach to prevent complications of disease and treatment (Fig. 349-2, and Table 349-5, in HPIM-20). As SLE predominantly affects young women, teratogenic potential and need for effective contraception must be considered with each prescribed medication.
CONSERVATIVE THERAPIES FOR NON-LIFE-THREATENING DISEASE